Study of Sirolimus Therapy for Segmental Overgrowth Caused by Somatic PI3K Activation
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|ClinicalTrials.gov Identifier: NCT02428296|
Recruitment Status : Completed
First Posted : April 28, 2015
Last Update Posted : August 9, 2018
- PIK3CA-related overgrowth spectrum (PROS) is caused by changes in the PIK3CA gene. This gene makes a protein that communicates with other proteins in the body to cause cells to grow. Alterations in PIK3CA change the chemical signals in the body and cause overgrowth in fatty, vascular and other tissues. Sirolimus is a drug that reduces the signals sent by one of the proteins in this chemical signaling pathway. Researchers want to learn whether the drug sirolimus can reduce or stabilize some of the overgrowth that patients with PROS experience.
- To measure how the overgrowth of patients with PROS changes over time and whether taking a drug called sirolimus can reduce or stabilize a person s overgrowth.
- People ages 3 to 65 years old with a confirmed mutation or alteration of the PIK3CA gene in the person s affected tissues (a somatic mutation).
- Participants will be screened with medical history and genetic counseling.
- First 6 months: Participants will have their overgrowth monitored.
- Next 6 months: Participants will take sirolimus once or twice a day.
- Participants will have to visit the clinic several times, and stay in the area for 4 5 days each time.
- Participants will have a one month-long visit to the clinic.
- During clinic visits, participants will have:
- Blood and urine tests.
- Photographs of their physical features.
- Scans, including an MRI and DEXA, and possibly x-rays and CT scans.
- For the MRI and CT scans, participants will lie in a machine that takes pictures of their body.
- The DEXA involves a small amount of radiation.
- They may have:
- Non-invasive heart function tests.
- Lung function tests.
- Participants will have several blood and urine tests between visits.
- Participants will complete surveys and keep a diary of their treatment and side effects.
- Participants may visit other health specialists or undergo other tests based on side effects.
- One month after stopping the study drug, participants will have 1 clinic visit.
|Condition or disease||Intervention/treatment||Phase|
|PIK3CA-Related Overgrowth Spectrum (PROS) Growth Disorder Genetics||Drug: Sirolimus||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Nonrandomized Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Caused by Somatic PI3K Activation|
|Study Start Date :||April 23, 2015|
|Actual Primary Completion Date :||February 14, 2018|
|Actual Study Completion Date :||February 14, 2018|
- Drug: Sirolimus
Low dose sirolimus will be given in daily dosing to achieve trough levels of 2-6 ng/ ml.
- The primary outcome measures will use quantitative MRI scan of the affected and unaffected body part (s) to demonstrate negativechange in fibrofatty, muscular, and/or bony overgrowth. [ Time Frame: At 0, 6, 9, 12 months ]
- A second primary outcome measure will evaluate use of Dual-energy Xray Absorptiometry (DXA) for body composition to demonstatereduction in fibrofatty overgrowth. [ Time Frame: At 0, 6, 9, 12 months ]
- The third primary outcome measure will evaluate the use of measurements on physical examination of affected body part(s). [ Time Frame: 0, 6, 6 1/2, 7, 9, 12 mos ]
- To establish optimal sirolimus dosing algorithms for a future RCT. [ Time Frame: 12 mons ]
- To evaluate alternative treatment outcomes for inclusion as primary or secondary end-ppoints in a future RCT e.g. quality of life measures(both subjective and observational) in the pre- and post-treatment periods [ Time Frame: 0, 6, 7, 9, 12 mos ]
- To establish if inter-patient comparison will be feasible in a future RCT. [ Time Frame: 12 mons ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02428296
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Kim M Keppler-Noreuil, M.D.||National Human Genome Research Institute (NHGRI)|